The foam fractionation column was set up to enable the separation of methylene blue dye (MB) by utilizing sodium dodecyl sulfate (SDS) as a surfactant that serves as a collector. The effect of operating variables like SDS dosage, pH, air flow rate, liquid loading, and dye concentration was examined on percentage removal, enrichment ratio, and surface excess. Experiments were designed based on the Box-Behnken methodology. Response surface methodology was then implemented to investigate the interaction effects between the operating variables on response namely percentage removal and enrichment ratio. The accuracy of the mathematical model developed was asserted by higher values of the regression coefficient (0.962 for percentage removal and 0.969 for enrichment ratio). Further, the grey relational analysis tool was applied for the estimation of the optimum operating variable's values to obtain maximum percentage removal and enrichment ratio. The optimum values came out to be: air flow rate 150 mL min(-1); liquid loading 600 mL, and dye concentration 35 mL min(-1), respectively, at 95.8% removal with enrichment ratio of 7.7.